Zika Virus Epidemic in Brazil. II. Post-Mortem Analyses of Neonates with Microcephaly, Stillbirths, and Miscarriage

Azevedo, Raimunda do Socorro da Silva; Araújo, Marialva Tereza Ferreira de; Oliveira, Consuelo Silva de; Filho, Arnaldo Jorge Martins; Nunes, Bruno Tardelli Diniz; Henriques, Daniele Freitas; Silva, Eliana Vieira Pinto da; Carvalho, Valéria Lima; Chiang, Jannifer Oliveira; Martins, Lívia Carício; Vasconcelos, Barbara Cristina Baldez; Sousa, Jorge Rodrigues de; Araújo, Fernanda M. C.; Castro, Andressa R. P; Queiroz, Maria Goretti; Verotti, Mariana Pastorello; Nunes, Márcio Roberto Teixeira; Cruz, Ana Cecília Ribeiro; Rodrigues, Sueli Guerreiro; Shi, Pei–Yong; Quaresma, Juarez Antônio Simões; Tesh, Robert B.; Vasconcelos, Pedro Fernando da Costa

doi:10.3390/jcm7120496

“…For the analysis of fetal tissue samples for viral RNA, we started our analysis with the control fetuses and tested 26 fetal and MFI tissues, consisting of tissues most likely to contain viral RNA based on our prior study (11). Next we generated a heatmap and selected a list of 17 tissues consisting of those most likely to be infected and diagnosed the most infections in the control fetuses, with addition of brain regions most likely to have histological lesions in the current study (such as hippocampus), or found to be infected in human fetuses affected by CZS (51). The criteria to define infection were used systematically for both control and antibody-treated group fetuses: a fetus was considered ZIKV infected if at least one tissue had a consistent qRT-PCR signal (3/3 replicates positive for viral RNA); this situation applied to 11 of the 12 control fetuses.…”

Section: Macaque Infection Experimentsmentioning

confidence: 99%

A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques

Rompay

¹

,

Coffey

²

,

Kapoor

³

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement (ADE) in vitro and extend their half-lives. Here we report on prophylactic coadministration of the Fc-modified antibodies to pregnant rhesus macaques challenged three times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission, protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV.

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“…For the analysis of fetal tissue samples for viral RNA, we started our analysis with the control fetuses and tested 26 fetal and maternal-fetalinterface (MFI) tissues, consisting of tissues most likely to contain viral RNA based on our prior study (11). Next we generated a heatmap and selected a list of 17 tissues consisting of those most likely to be infected and diagnosing the most infections in the control fetuses, with addition of brain regions most likely to have histological lesions in the current study (such as hippocampus), or found to be infected in human fetuses affected by CZS (50). The criteria to define infection were used systematically for both control and antibody treated group fetuses: a fetus was considered ZIKV-infected if at least one tissue had a consistent qRT-PCR signal (3/3 replicates positive for viral RNA); this situation applied to 11 of the 12 control fetuses.…”

Section: Isolation and Quantitation Of Viral Rna From Fluids And Tissmentioning

confidence: 99%

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Rompay¹,

Coffey²,

Kapoor

³

et al. 2020

Preprint

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Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmissionand fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV. Significance statement:Zika virus (ZIKV) infection during pregnancy can cause fetal abnormalities. Vaccines against ZIKV are under development, but because of potential safety concerns due to disease enhancing antibodies, and the time required by active immunization to induce protective antibodies, there is a need to explore alternative strategies. Recombinant monoclonal antibodies can be modified to prevent enhancement of infection, and thus could be an efficacious and safe alternative to vaccines to confer rapid protection. We show that prophylactic administration of two engineered antibodies, Z004 and Z021, to pregnant macaques partially protects against fetal neurologic damage and limits vertical transmission of ZIKV.

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“…Such infectious agents include viruses which can negatively impact pregnancy, being linked to miscarriage and other outcomes such as stillbirth and preterm delivery [ 18 , 21 ]. A number of human viruses, including herpes simplex viruses 1 and 2, cytomegalovirus, dengue virus, zika virus, adenovirus, and adeno-associated virus can potentially infect the placenta, the trophoblast, and/or the cytotrophoblasts after viremia or an ascendant infection [ 18 , 22 , 23 , 24 , 25 , 26 , 27 ]. It is known that cytomegalovirus and herpes simplex viruses can cross the placental barrier, thereby resulting in either SA events or severe birth defects, such as microcephaly [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation on Spontaneous Abortion and Human Papillomavirus Infection

Tognon

¹

,

Tagliapietra

²

,

Magagnoli

³

et al. 2020

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Viral infections are considered to be risk factors for spontaneous abortion (SA). Conflicting results have been reported on the association between Human Papillomavirus (HPV) and SA. HPV DNA was investigated in matched chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from women who experienced SA (n = 80, cases) and women who underwent a voluntary interruption of pregnancy (VI; n = 80, controls) by qualitative PCR and quantitative droplet digital PCR (ddPCR). Viral genotyping was performed using real-time PCR in HPV-positive samples. Specific IgG antibodies against HPV16 were investigated in sera from SA (n = 80) and VI (n = 80) females using indirect ELISA assays. None of the DNA samples from SA subjects was HPV-positive (0/80), whilst HPV DNA was detected in 2.5% of VI women (p > 0.05), with a mean viral DNA load of 7.12 copy/cell. VI samples (n = 2) were found to be positive for the HPV45 genotype. The ddPCR assay revealed a higher number of HPV-positive samples. HPV DNA was detected in 3.7% and 5% of SA and VI chorionic tissues, respectively, with mean viral DNA loads of 0.13 copy/cell in SA and 1.79 copy/cell in VI (p >0.05) samples. All DNA samples from the PBMCs of SA and VI females tested HPV-negative by both PCR and ddPCR. The overall prevalence of serum anti-HPV16 IgG antibodies was 37.5% in SA and 30% in VI (p > 0.05) women. For the first time, HPV DNA was detected and quantitatively analyzed using ddPCR in chorionic villi tissues and PBMCs from SA and VI women. Circulating IgG antibodies against HPV16 were detected in sera from SA and VI females. Our results suggest that HPV infection in chorionic villi may be a rare event. Accordingly, it is likely that HPV has no significant role in SA.

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Zika Virus Epidemic in Brazil. II. Post-Mortem Analyses of Neonates with Microcephaly, Stillbirths, and Miscarriage

Cited by 24 publications

References 28 publications

A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques

A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Investigation on Spontaneous Abortion and Human Papillomavirus Infection

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